RESUMEN
Diabetic cardiomyopathy (DCM) is a serious common complication of diabetes. Unfortunately, there is no satisfied treatment for those patients and more studies are in critical need to cure them. Therefore, we aimed to carry out our current research to explore the role of two novel therapeutic approaches: one a biological drug aimed to block inflammatory signaling of the IL 1beta (IL1ß) axis, namely, anakinra; the other is provision of anti-inflammatory regenerative stem cells. Wistar male rats were allocated into four groups: control group: type 2 diabetes mellitus (DM) induced by 6-week high-fat diet (HFD) followed by a single-dose streptozotocin (STZ) 35 mg/kg i.p., then rats were allocated into: DM: untreated; DM BM-MSCs: received a single dose of BM-MSCs (1 × 106 cell/rat) into rat tail vein; DM-Anak received Anak 0.5 µg/kg/day i.p. for 2 weeks. Both therapeutic approaches improved cardiac performance, fibrosis, and hypertrophy. In addition, blood glucose and insulin resistance decreased, while the antioxidant parameter, nuclear factor erythroid 2-related factor 2 (Nrf2) and interleukin 10 (IL10), and anti-inflammatory agent increased. Furthermore, there is a significant reduction in tumor necrosis factor alpha (TNFα), IL1ß, caspase1, macrophage marker CD 11b, inducible nitric oxide synthase (iNOS), and T-cell marker CD 8. Both Anak and BM-MSCs effectively ameliorated inflammatory markers and cardiac performance as compared to non-treated diabetics. Improvement is mostly due to anti-inflammatory, antioxidant, anti-apoptotic properties, and regulation of TNFα/IL1ß/caspase1 and Nrf2/IL10 pathways.
RESUMEN
The aim of this study was to investigate the effect of a regenerative therapy comprising mesenchymal stem cells (MSCs) pretreated with melatonin (MT) as a new therapy for underlying diabetic nephropathy (DN) pathogenesis in a rat model, and its possible effect on autophagy protein Beclin-1. Forty adult male albino Wistar rats were distributed among 4 groups: (i) control, (ii) DN, (iii) MSC-treated, and (iv) treated with MSCs that were pre-incubated in-vitro with MT (5 µmol·L-1 for 24 h; MSCs + MT). MSCs treatment significantly improved the renal functions and ameliorated the measured underlying DN pathogenesis and elevation of Beclin-1 protein levels compared with the DN group. In-vitro pretreatment of MSCs with MT enhanced proliferation and efficiency, and thus improved the kidney functions by increasing superoxide dismutase (SOD-1) and Beclin-1, and decreasing transforming growth factor (TGF-ß) markers in the kidney tissue, compared with the MSC group (P < 0.05). In conclusion: MSCs represent a promising target in DN management, and their effect can be intensified by pretreatment with MT. The elevated levels of Beclin-1 could be a mediator.
